H1N1 Influenza vaccine manufacturers ramp up for October 15

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Rod Raynovich

As health officials in the Northern Hemisphere mobilize for the annual influenza season compounded by the pandemic H1N1 (Swine) Flu, production of a new vaccine looms critical. Last week the WHO said that H1N1 Flu is already spreading in India, Thailand and Vietnam coinciding with the monsoon season. Transmission has already peaked in the Southern Hemisphere and as of August 13 the WHO said over 182,166 cases have been reported worldwide with 1799 deaths. Earlier assessments of Swine Flu have not changed, i.e. that the virus is transmitted easily but is less lethal than past pandemic viruses. However scientists and health officials will be carefully monitoring virus mutation and will urge enhanced surveillance and report any unusual syndromes and side effects with new vaccines. Eurosurveillance.org estimates that H1N1 flu should dominate over seasonal flu in Germany this season.

HHS Secretary Katherine Sebelius and Commerce Secretary Gary Locke said on August 19 that risk groups-health workers, young children, elderly etc.- should get their seasonal flu virus vaccine immediately even though it does not have the H1N1 component.

Also employers should be flexible on absentee policies and send a message to employees that individuals who may be sick should stay home.

Five target population groups have been identified for the H1N1 vaccine that should be available by October 15. (See the August 19 Guidance for Employers to Plan for 2009-2010 Influenza Season at www.flu.gov).

Vaccine Update

Seven manufacturers in the late stages with clinical trials and manufacturing of the vaccine utilizing traditional vaccine technology in order to determine safety and whether two doses are needed. At least five countries have trials underway.

The formulation change for the upcoming season in the US would be to add the H1N1 flu strain (strain change) to the seasonal lflu vaccine.

For pandemic use in Europe, a number of vaccines are under development which utilize an adjuvant that was extensively tested for prototypes of H1N5 (Avian Flu) vaccines in 2007. Forty million doses of adjuvanted vaccines have already been in use in Europe for H5 with no safety concerns. Adjuvanted flu vaccines have never been registered or licensed in the US. (WHO Virtual Press Briefing August 6, 2009)

Manufacturers have begun to submit dossiers to regulators that may be authorized for use in September with more widespread release in October

There have been safety concerns about the Flu vaccine but the WHO position is that it is not possible to have a zero safety concern so there will be adverse events experienced by some people.

Availability of the vaccine may be limited so it will be important to target populations most at risk. Some experts are recommending vaccination of 55 million school age children to stop the Flu from spreading. In a study published in Lancet, CDC scientists found pregnant women most at risk. The WHO said One Billion doses of swine vaccine have been ordered and that there will be limited supply in the early days. US health officials recently estimated that just 45 million of 195 million doses ordered will be delivered by mid-October.

Antiviral Drugs

Partly out of concern for developing resistance to these drugs, the WHO and CDC are cautious on overuse of antivirals (TamiFlu and Relenza neuraminidase inhibitors) except in the most severe cases or those at risk for complications. Roche Holding the Tamiflu manufacturer said, Antivirals need not be administered for otherwise healthy individuals with mild flu-like symptoms.

Rapid Diagnostic Tests

In a recent report by the CDC and with limited data, three rapid diagnostic tests (RIDTs) for H1N1 Flu are relatively insensitive for detecting H1N1 virus when viral titers were low compared to the standard molecular test real time reverse transcription-polymerase (RT-PCR) chain reaction. With higher titers of virus the sensitivity of the three tests were 89-100% but with lower titers the sensitivity declined to 40-69% for the three tests by Inverness, Becton-Dickinson and Quidel. Specimen collection for rapid tests can be critical to sensitivity. The rapid tests are antigen tests that detect influenza viral nucleoprotein antigen. None of these FDA approved tests can distinguish between Influenza A subtypes. So while these tests can provide useful information that can impact healthcare it is important to understand their limitations. Interim guidance was provided by the CDC on August 10, 2009.

Several biotech companies have recently released news on the influenza front among them:

Biocryst (BCRX): Biocryst is in Phase II and pivotal trials for an IV and IM drug called Permivir, a neuraminidase inhibitor with partner Shionogi.Positive Phase III clinical results were reported in July.

Crucell (CRXL): Crucell announced this week an NIH/NIAID contract worth up to $40.7M aimed at advancing the development of monoclonal antibodies for the treatment of seasonal and pandemic influenza. The Company is also in a Phase II study of a cell culture based seasonal flu vaccine based on their PER.C6 technology which makes production of large amounts of vaccine possible. The Company has HHS funding and is partnered with Sanofi Pasteur.

Enigma Diagnostics: Have an Agreement with GlaxoSmithKline to develop point of care PCR tests to identify specific influenza strains.

NovaVax: NVAX announced positive pre-clinical results with a novel H1N1 influenza virus-like particle (VLP) vaccine in ferrets, which Novavax believes is the most appropriate animal model for evaluating influenza diseases and vaccines. A Phase II study of a trivalent VLP vaccine is underway.

Seegene (Private South Korea and MD): Working on a multiplex PCR test for hospitals that can identify influenza subtypes and antiviral drug sensitivity.